Acquired Hypothyroidism: Causes, Effects, and Treatment

Acquired hypothyroidism develops when the thyroid gland fails to produce enough hormones, disrupting metabolism and overall health. This condition can result from autoimmune disorders, iodine deficiency, or medical treatments affecting the thyroid. While more common in adults, it can also occur in children, impacting growth and development.

Early diagnosis and treatment are essential to prevent complications. Proper management restores hormone levels, alleviates symptoms, and reduces long-term health risks.

Basic Thyroid Gland Function

The thyroid gland, a butterfly-shaped organ at the base of the neck, regulates metabolism by producing thyroxine (T4) and triiodothyronine (T3). These hormones, derived from dietary iodine, influence nearly every cell in the body. Their production is controlled by the hypothalamic-pituitary-thyroid (HPT) axis. The hypothalamus releases thyrotropin-releasing hormone (TRH), prompting the pituitary gland to secrete thyroid-stimulating hormone (TSH), which stimulates the thyroid to release T4 and T3. While T4 is the primary hormone, it is converted into the more active T3 in peripheral tissues.

T3 binds to nuclear receptors in target cells, regulating gene expression and driving metabolic processes. These hormones influence basal metabolic rate, thermogenesis, cardiovascular function, and lipid metabolism. They enhance mitochondrial activity, increasing oxygen consumption and heat production to maintain body temperature. In the cardiovascular system, they upregulate beta-adrenergic receptors, increasing heart rate and cardiac output. Additionally, they promote cholesterol and triglyceride breakdown, preventing excessive lipid accumulation.

Beyond metabolism, thyroid hormones support neurological function, musculoskeletal health, and digestion. They help maintain neurotransmitter balance, affecting memory, mood, and concentration. In skeletal muscle, they regulate protein turnover, ensuring strength and coordination. They also assist in gut motility, preventing constipation and slowed digestion. Disruptions in hormone levels lead to widespread physiological imbalances, emphasizing the importance of maintaining optimal thyroid function.

Causes and Risk Factors

Acquired hypothyroidism arises from various factors that impair thyroid hormone production. A primary cause is iodine deficiency, which hinders the synthesis of thyroxine (T4) and triiodothyronine (T3). Since iodine is essential for hormone production, insufficient intake leads to reduced hormone levels and compensatory thyroid gland enlargement (goiter). The World Health Organization (WHO) identifies iodine deficiency as a significant public health concern, particularly in areas without iodized salt programs. Even mild insufficiency can result in subclinical hypothyroidism, which may progress to overt deficiency.

Medical treatments can also induce hypothyroidism. Radioactive iodine therapy, commonly used for hyperthyroidism or thyroid cancer, destroys thyroid tissue, often leading to permanent hormone deficiency. Similarly, surgical removal of the thyroid gland necessitates lifelong hormone replacement. Certain medications, including amiodarone, lithium, and tyrosine kinase inhibitors, can disrupt hormone synthesis and iodine metabolism. A meta-analysis in The Journal of Clinical Endocrinology & Metabolism found that long-term lithium therapy increases hypothyroidism risk by inhibiting hormone release and altering iodine uptake.

Environmental toxins further contribute to thyroid dysfunction. Endocrine-disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs), bisphenol A (BPA), and per- and polyfluoroalkyl substances (PFAS) interfere with hormone synthesis, transport, and receptor activation. A study in Environmental Health Perspectives linked high PFAS exposure to lower thyroid hormone levels and increased hypothyroidism risk, particularly in populations with prolonged exposure to contaminated water or industrial pollutants.

Effects on Body Systems

Acquired hypothyroidism affects multiple organ systems due to the essential role of thyroid hormones in cellular metabolism. In the cardiovascular system, reduced hormone levels decrease heart rate, cardiac output, and vascular elasticity. Increased systemic vascular resistance raises blood pressure and atherosclerosis risk, as thyroid hormones normally promote nitric oxide production for vasodilation. Severe cases may lead to pericardial effusion, where fluid accumulates around the heart, impairing function.

Neurological effects include cognitive slowing, memory impairment, and depressive symptoms. These result from diminished neurotransmitter synthesis and impaired synaptic plasticity. Functional MRI studies show reduced activity in the prefrontal cortex and hippocampus of hypothyroid patients, correlating with deficits in executive function and memory. Slowed nerve conduction also contributes to peripheral neuropathy, causing numbness, tingling, and muscle weakness. In older adults, untreated hypothyroidism increases the risk of dementia-like symptoms.

The musculoskeletal system also suffers, as thyroid hormones regulate bone turnover and muscle protein synthesis. Reduced osteoclastic and osteoblastic activity slows bone remodeling, increasing osteopenia and osteoporosis risk, particularly in postmenopausal women. Muscle metabolism impairment leads to myopathy, with stiffness, cramps, and weakness. Elevated creatine kinase levels in hypothyroid patients indicate muscle cell damage and reduced mitochondrial efficiency. These complications contribute to chronic fatigue and reduced mobility.

Clinical Manifestations

Symptoms of acquired hypothyroidism develop gradually as hormone levels decline. Fatigue is often the earliest sign, caused by reduced cellular energy production. Patients report persistent exhaustion despite adequate rest, linked to impaired mitochondrial function and ATP synthesis. Cognitive difficulties, including memory lapses and difficulty concentrating, are common and can interfere with daily activities.

As metabolism slows, thermoregulation becomes impaired, leading to increased sensitivity to cold. Individuals may layer clothing even in mild temperatures due to diminished heat generation. Skin changes include dryness and pallor from decreased gland activity and circulation. In some cases, myxedema develops, causing swelling from glycosaminoglycan accumulation in the dermis. Hair and nail growth slow, leading to brittle nails and thinning hair, especially along the lateral eyebrows.

Diagnostic Evaluations

Diagnosing acquired hypothyroidism requires clinical assessment and laboratory testing. Physicians take a detailed medical history and conduct a physical exam, looking for signs such as dry skin, bradycardia, weight gain, and delayed reflexes. Given the nonspecific nature of symptoms, lab tests confirm the diagnosis.

The primary test is serum thyroid-stimulating hormone (TSH), a sensitive marker of thyroid function. Elevated TSH indicates the pituitary is compensating for inadequate hormone production, signaling primary hypothyroidism. Low or inappropriately normal TSH with hypothyroid symptoms suggests secondary hypothyroidism due to pituitary or hypothalamic dysfunction.

Free thyroxine (FT4) levels help assess thyroid hormone status. A high TSH with low FT4 confirms overt hypothyroidism, while mildly elevated TSH with normal FT4 suggests subclinical hypothyroidism. Additional tests may include triiodothyronine (T3) levels, though T3 often remains normal until late-stage disease. Testing for thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies helps identify Hashimoto’s thyroiditis, the most common autoimmune cause. Thyroid ultrasound may assess gland size and detect structural abnormalities if nodules or goiter are present. In rare cases, a radioactive iodine uptake scan differentiates thyroid disorders, though it is more relevant in hyperthyroid conditions.

Hormonal Replacement Options

Treatment for acquired hypothyroidism involves hormone replacement therapy to restore normal function. The standard therapy is levothyroxine, a synthetic T4 that mimics natural hormone production. Once ingested, it converts to T3 in peripheral tissues, ensuring proper metabolic activity. Dosage is individualized based on age, weight, severity, and health conditions. Physicians start with a conservative dose in older adults or those with heart disease to prevent overstimulation. Regular TSH and FT4 monitoring ensures effective dosing while avoiding overtreatment, which can lead to hyperthyroid symptoms like palpitations and anxiety.

While levothyroxine is the preferred therapy, some patients report persistent symptoms despite normal TSH levels. In such cases, combination therapy with liothyronine (T3) may be considered, though its effectiveness remains debated due to concerns about fluctuating hormone levels and cardiovascular risks. Some studies suggest improved mood and cognitive function in select patients, while others find no advantage over T4 monotherapy.

For individuals with absorption issues, alternative formulations such as liquid levothyroxine or soft gel capsules may improve bioavailability. Consistency in dosing—taking medication on an empty stomach with water—enhances absorption and therapeutic efficacy.